We have used a set of identified cells (the touch cells) in the nematode Caenorhabditis elegans to examine questions of genetic specification of cell differentiation. Over 350 mutations that map to at least 16 loci have been identified that affect, most in a cell-specific manner, the function and development of the touch cells or their precursors. In addition, we have demonstrated that the mature structure of these cells results from extrinsic interactions as well as apparently intrinsic factors. In this proposal we describe experiments to extend these findings to learn how the differentiated characteristics of the touch cells are expressed. The specific aims of the proposal are: 1) to continue to characterize previously identified genes that affect the touch cells by screening for new mutant alleles of specific genes ("precomplementation"), nonsense mutations, and deletions; 2) to identify genes that affect touch cell development yet either do not affect touch cell function or produce such severely defective animals that the function cannot be tested; 3) to characterize these genes at the molecular level by the isolation and study of the DNA from these genes; 4) to localize the activity of these genes temporally and spatially by mosaic analysis and in situ hybridization to mRNA; and 5) to investigate the affect of other cells on the development of the touch cells by laser killing of specific target and associated cells. The health relatedness of this reserch derives from its contribution to an understanding of basic cellular and developmental control mechanisms used in higher organisms and, perhaps, man.